The purpose of this project is to increase our understanding of the metabolism of retinoids. Such information must be had before a rational approach can be taken to the design of new retinoids with greater activity in the reversal of preneoplasia in epithelial tissues. The investigation is along two basic lines: 1) The study of the in vitro metabolism of retinoic acid and synthetic retinoids in subcellular systems of target tissues as compared to non-target tissues, and 2) the study of the biochemical activation mechanisms of the synthetic retinoids.